More than 1 million cases of basal cell or squamous cell cancer will be diagnosed annually. The most serious form of skin cancer, malignant melanoma, is expected to be diagnosed in 59,580 persons in 2005 in the US. Since 1981, the incidence of melanoma has increased approximately 3% per year. Melanoma is the most common cancer among people 25 to 29 years old. The three major types of skin cancer are basal cell carcinoma, squamous cell carcinoma, and melanoma.
Although melanoma accounts for only 4% of all dermatological cancers, it causes more than 75% of all deaths related to skin cancer (Miller and Mihm, 2006, N Engl J Med, 355, 51-65). Metastatic melanoma can spread to other organs than the skin, most commonly the lungs and liver. The survival rate for patient with metastatic melanoma is 14% and. However if malignant melanoma is diagnosed at an early stage, it can usually be cured, but melanoma diagnosed at a late stage is more likely to spread and cause death. Early detection increases 5 year survival rate from 14% to 98% for melanoma. It is therefore exceedingly important to make efforts to improve early detection of melanoma.
Examination of the Skin by Patients and General Physicians
The only and best way to detect early skin cancer is to examine the skin (Rhodes, 2006, Dermatol Ther, 19, 50-69). Periodic self-examination of the skin, and examination of the skin is potentially life saving. A single case-control study has demonstrated a 63% reduction in mortality associated with monthly skin self-examination (Berwick, Begg, Fine, Roush and Barnhill, 1996, J Natl Cancer Inst, 88, 17-23). The prevalence of whole-body skin self-examination is relatively low even among populations at very high risk for skin cancer. Even more disappointing than the total lack or infrequent use of self-examination for suspicious skin lesions among lay persons is the relatively low frequency of whole-body skin examinations by primary practice physicians, or physician recommendations to patients that they self-examine their skin for suspicious lesions (Friedman, Whitaker-Worth, Grin and Grant-Kels, 2004, Cutis, 74, 305-11, Weinstock, Martin, Risica, Berwick, Lasater, Rakowski, Goldstein and Dube, 1999, Am J Prev Med, 17, 169-75). Skin awareness, self-examination of the skin, examination of the skin and physician examination of the skin are intervention strategies that are likely to have immediate positive impact on skin-cancer—specific mortality. Skin self-examination and examination by family members are likely to enhance the possibility of early diagnosis given the fact that patients or acquaintances suggest the diagnosis of skin-cancer about 75% of the time, whereas physicians suggest the diagnosis only 25% of the time (Epstein, Lange, Gruber, Mofid and Koch, 1999, Jama, 281, 640-3). Thus, examination of the skin at periodic intervals is central to any intervention program to reduce skin-cancer—specific mortality (Rhodes, 2006, Dermatol Ther, 19, 50-69).
The common scenario for skin cancer detection in 75% of the cases is primary detection by the individual, who then approach a health professional for opinion and evaluation. The health professional will examine skin by eyeballing or if available by dermoscopy in an attempt to properly access the presence of cancer cells (Bauer, Blum, Strohhacker and Garbe, 2005, Br J Dermatol, 152, 87-92). If he or she suspects cancer, a biopsy of the affected skin is needed to make a diagnosis. For this, the health professional will remove a sample of tissue, and a pathologist will examine it under a microscope to check for cancer cells. Currently 30 moles are removed per malignant mole for diagnostic purposes of skin cancer lesions. Methods to improve the evaluation of the neoplastic properties of melanoma cells and reduce unnecessary excision of benign melanocytic naevi are needed.
Current Methods of Detection of a Skin Cancer
Melanoma is a usually fatal skin cancer, unless it is detected and surgically removed in its earliest stages. Early detection of malignant melanoma is difficult because early melanomas, those having a Breslow thickness less than 1 mm, share many diagnostic features with benign lesions, such as dysplastic nevi or atypical melanocytic nevi.
Detection of a skin cancer such as melanoma is typically carried out by physical examination of the skin followed by biopsy of selected lesions suspected to be cancerous. The effectiveness of this procedure is dependent on the experience of the examiner, and errors in diagnosis can be fatal. Occasionally, cancers have remained undetected which metastasize beyond the original site of occurrence and lead to a decrease in survival. On the other hand a 30 fold biopsies of skin lesions occur which are not cancerous. Thus high frequencies of unnecessary surgical procedures occur. On several occasions the biopsy is carried out in the skin of the facial region and may result in some incidents of cosmetic scarring.
When an individual is diagnosed with skin cancer the physician determines if the cancer can be removed by surgery. Individuals with local disease may be cured by complete resection of the tumor. Prior to the surgery, evaluation of the spread of the tumor is conducted using X-rays, CT scans, MRI scans or PET images. These tests provide guidance prior to the surgery. During surgery, the surgeon relies on the evaluation of the pathologist to determine, real time the spread of the cancer. This procedure requires a highly trained pathologist to be present at the surgery and to rapidly analyze the tissue sample while the patient remains on the operating table. If the cancer has a great spread than anticipated, the surgeon continues to try to remove any residual tumor cells from the site intervention. In 15-25% of the incidents, residual diseased cells may remain on site in the patient. These individuals have a lower survival rate greater than those that have the tumor completely removed.
Several approaches using radioactive isotopes or photo-sensitizers linked to targeting entities have been conducted to determine the spread of the lesion. These detection methods are limited and cannot be used by the general physician's practice for screening individuals nor can they be used to determine the extent of the cancer lesion. Some detection methods are described in U.S. Pat. Nos. 6,256,530, 6,091,985, 6,083,487; EP patent publication No. 0588994 A1.